The study of mutations generated in a highly mutable strain of Drosophila melanogaster has shown that insertion of the retrovirus-like transposon gypsy into various chromosomal sites accounts for a high proportion of the mutation events. Historically a number of spontaneous mutations are known to be due to the insertion of gypsy. In general, these have been very stable mutations, thus it is of considerable interest to determine the conditions under which gypsy becomes highly amplified and mobilized. Genetic, cytological and molecular studies of stable strains show that the transposon is usually found in low copy number (3-4) per genome but in the unstable strain some sublines show fifty to sixty copies. High copy number cannot account entirely for the instability since some highly mutable sublines have become stable in a single generation, though they still harbor a number of copies of gypsy. In crosses of stable by unstable lines only the F1 females exhibit amplification and mobilization of gypsy. This occurs early in embryogenesis, so that mutations occur as mosaics in both somatic and germinal tissues. Curiously both male and female offspring of these F1 females continue for a number of generations to show high mutation rates, while F1 males and their offspring show no mobilization of gypsy and are mutationally stable. We are attempting through various crosses and by molecular characterization of the transposons to discover the conditions that bring stability or that cause a stable strain to mobilize and amplify the transposons.